We are requesting funding for a NanoSIMS 50L Ion Micro-Analyzer, a new generation of secondary ion mass spectrometer. This instrument is at the core of Multi-Isotope Imaging Mass Spectrometry (MIMS), a revolutionary technology pioneered in our National Resource for Imaging Mass Spectrometry (NRIMS, NIBIB/NIH) (Lechene et al. 2006, J. Biol: 5:20; Lechene et al. 2007, Science, 317:1563). MIMS allows comparison at a subcellular level of the distribution and measurement of several molecules labeled with different stable isotopes at exactly the same location. With MIMS, for the first time, one can both see (at high resolution) and measure (with high precision) in subcellular compartments of individual cells components and processes that have not before been seen or measured. Intracellular isotope quantitative imaging is applicable to an immense array of molecules, which may be labeled with any stable (or radioactive) isotope and will contribute to studies in all domains of biomedical research. We will continue to pioneer MIMS in collaboration with researchers in cell biology, biochemistry, cardiology, nephrology, immunology, transplantation,stem cell, cancerology, infectious disease, microbiology and virology. Our aims are to study the localization and the turnover of proteins, fatty acids, sugars, foreign molecules, and the localization of drugs in cellular micro domains; nitrogen fixation and microbe metabolism; virus penetration; DNA replication in symmetric and asymmetric division; cell lineage , the migration of donor cells to receiver niches, the nesting of stem cell. MIMS biomedical applications will continue to expand. Stable isotopes are invaluable for human studies. MIMS can detect any isotope label, thus providing a technique for following the cellular incorporation of labeled metabolic precursors or drugs in the numerous situations where radiolabels cannot be used. Tagging cellular DNA with stable isotopes allows one very long-term and risk-free tracking of cells. This provide a most powerful method for the study of cell migration, cell exchange between a host and a donor, identification of stem cells and cell tumor metastasis. Finally, as quoted in J. Weitzman Research News article (2006, J. Biol. 5:16): The most significant feature of this technique is that it opens up a whole new world of imaging; we haven't yet imagined all that we can do with it. The novelty of the technique means it will take some time for the details to be absorbed, [but it] sets a spectacular new standard for spatial resolution and detection of stable and radioactive compounds in cells. PUBLIC HEALTH RELEVANCE Called 'an imaging revolution' as quoted by J. Weitzman (2006, J. Biol. 5:16), MIMS will help solve intractable problems in all fields of biomedical research. [unreadable] [unreadable] [unreadable]